Our project addresses key issues in adult-to-adult living donor liver transplantation (LDLT). The Main Trial is an extension of the ongoing A2ALL Study - our program is an active participant and the leading enroller of patients to this trial. The current application indicates that we intend to continue to participate, accrue, and enroll patients to the trial. In the Main Trial, we will compare outcomes of LDLT recipients to the outcomes of contemporaneously studied patients undergoing deceased donor liver transplantation (DDLT). Also, in this Trial, we will conduct longitudinal long-term assessment of donors and donor controls - for the purpose of assessing the impact of donor hepatectomy and living donation on subsequent health, quality of life, and psycho-social function of donors. We propose to continue the LADR-A2ALL protocol for pre-transplant antiviral treatment of patients with chronic hepatitis C in order to prevent recurrence of hepatitis C in the allograft post-transplant. However, virologic responses in patients infected with genotype 1 HCV are inadequate to boost response in these patients and increase the efficacy of LADR-A2ALL we propose the addition of strategically-targeted-antiviral-therapies against hepatitis C (STAT-C). We also propose to continue the study of return of hepatic function in donors after right lobectomy. In our modified protocol we specifically focus on volumetric studies of liver and spleen, SPECT liver-spleen scan, and dual-isotope-labeled cholate clearances and cholate shunt to assess the physiologic changes after hepatectomy. Two ancillary studies will focus on the long-term outcomes of donors and biliary complications in recipients of LDLT. A key concern of physicians, surgeons, patients and families is whether any aspect of donor health, function, psychological adjustment, or social status is affected by LDLT. Our study will use a combination of clinic visits and assessments coupled with telephone interviews to define donor status over 2 years post-hepatectomy. Recent publications and our own analyses suggest that biliary complications are more common and more severe in LDLT recipients. In our ancillary study of biliary complications, we will compare and contrast biliary complications and outcomes between LDLT and DDLT recipients. PUBLIC HEALTH RELEVANCE: The Colorado Transplant Center aims to define a number of key issues in LDLT - long-term outcomes of LDLT, compared to DDLT, efficacy and safety of pre-transplant antiviral therapy, changes in donor hepatic mass and hepatic function after right lobectomy, long-term followup of donors and matched potential-donor controls, and incidence and severity of biliary complications after LDLT. Methods will include CT or MRI measurement of liver volume. SPECT liver-spleen scan, stable isotopes, and LC/MS.